Mason D Y, Jones M, Goodnow C C
Nuffield Department of Pathology, John Radcliffe Hospital, Oxford, UK.
Int Immunol. 1992 Feb;4(2):163-75. doi: 10.1093/intimm/4.2.163.
To analyse mechanisms of immunological self-tolerance, a detailed comparison of the development and fate of lysozyme-specific B lymphocytes was carried out in transgenic mice expressing rearranged anti-lysozyme IgM/IgD Ig transgenes in the absence or presence of an additional transgene encoding lysozyme itself. In the absence of lysozyme, B cell development, localization, and differential expression of transgene-encoded IgM and IgD occurred in the normal sequence in Ig transgenic mice, establishing that these animals provide a physiological model for studies of B cell selection in vivo. By contrast, in lysozyme-expressing double-transgenic mice, tolerant lysozyme-reactive B cells persisted within the follicular mantle zones in the spleen, lymph nodes, and Peyer's patches, but were eliminated from the splenic marginal zones. It could be shown that lysozyme-binding and induction of tolerance occurred as soon as surface Ig was expressed on immature B cells in the bone marrow of the double-transgenic mice although this did not prevent maturation, emigration from the bone marrow, and localization in peripheral lymphoid follicles. These findings, together with recent examples of aborted maturation of self-reactive B cells, indicate two functionally distinct antigen receptor signalling events in immature B cells and suggest a unique role for the follicular microenvironment.
为了分析免疫自身耐受性的机制，在表达重排抗溶菌酶IgM/IgD Ig转基因的转基因小鼠中，在不存在或存在额外编码溶菌酶自身的转基因的情况下，对溶菌酶特异性B淋巴细胞的发育和命运进行了详细比较。在没有溶菌酶的情况下，Ig转基因小鼠中B细胞的发育、定位以及转基因编码的IgM和IgD的差异表达按正常顺序发生，这表明这些动物为体内B细胞选择的研究提供了一个生理学模型。相比之下，在表达溶菌酶的双转基因小鼠中，耐受的溶菌酶反应性B细胞持续存在于脾脏、淋巴结和派伊尔结的滤泡套区，但从脾边缘区被清除。可以证明，在双转基因小鼠的骨髓中，当未成熟B细胞表达表面Ig时，溶菌酶结合和耐受性诱导就会发生，尽管这并不妨碍成熟、从骨髓中迁出以及在外周淋巴滤泡中的定位。这些发现，连同最近自身反应性B细胞成熟受阻的例子，表明未成熟B细胞中存在两种功能不同的抗原受体信号事件，并提示滤泡微环境具有独特作用。
